This research program is primarily directed towards improving the efficacy of cancer treatment, through a better understanding of the biological factors involved in the response of normal and malignant tissues to treatment modalities. The experimental model systems developed over the years provide the opportunity for obtaining quantitative information at the biochemical, cellular, tissue and animal levels. These systems include the gastrointestinal epithelium, hematopoietic systems, immunological systems, a highly manipulative mastocytoma tumor, a viral leukemia, and the PDP assay for growth fraction measurements in experimental and human tumors. These cellular systems are being utilized to define the biological parameters in both normal and malignant tissues. Concurrently, cancer treatment regimens utilizing multifraction irradiation, chemotherapeutic agents, immune stimulation, and combination modality therapy are being quantitatively evaluated. Emphasis is placed on defining the normal tissue response to therapy, as well as the tumor response, such that therapeutic ratio considerations can be applied to various treatments. It is felt that an increased understanding of the cellular and tissue events occurring in both normal and malignant tissues, initially unperturbed and following treatment with currently available modalities, will provide a basis for planning cancer therapy regimens with a rational a priori input. These can then be evaluated quantitatively to assess their contribution towards improving the therapeutic ratio in the treatment of neoplastic disease.